Study On The Relationship Between Pathological Changes And Experessions Of EF-Tu_mt And EF-Ts(mt) In Human Brain With Refractory Temporal Lobe Epilepsy

Objective:Analyze the clinical features of 20 patients with refractory temporal lobe epilepsy.Observe the pathological changes and ultrastructure of 20 patients in experimental group. Examine the level of mitochondrial elongation factor in the brain of 20 patients in order to confirm the relationship between refractory temporal lobe epilepsy and mitocondrial elongation factor.Furthermore, explore the mechanism of temporal lobe epilepsy and provide theory basis for the new treatment of epilepsy.Background:When epilepsy happen, neurons demand more energy, which induce mitochondrial protein synthesis activity is hyperactive,and the protein participating in mitochondria translation increases accordingly, so EF-Tumt and EF-Tsmt, the important protein in mitochondria translation process, will change too. The expression of EF-Tumt and EF-Tsmt during epilepsy has been poorly understood until now. The animal experiments research in domestic and foreign countries has confirmed the expression of EF-Tumt and EF-Tsmt in status epilepticus experimental rats is higher than the control group significantly. However, there is seldom research evidence of EF-Tumt and EF-Tsmt in clinical trials.Therefore, it (?) to study advancely.Methods:20 patients with refractory temporal lobe epilepsy were selected as experimental group after the operation of epileptogenic focus resection from January in 2009 to January in 2011 in the first hospital of Jilin university. There were 11 male and 9 female, whose ages ranged from 16 to 58, with a mean of 27.7±11.14 years. The course of disease ranged from 2 to 29, with a mean of 9.45±7.67 years. The control group (n=6)was obtained from the normal temporal lobe cortex of the subjects. They had been enforced to debridement because of craniocerebral trauma and the subjects in control group had no past history of epilepsy or other neurologic diseases, and the pathological sections of specimens had been confirmed that the brain tissue structures were normal. There were 4 male and 2 female, whose ages ranged from 19 to 55, with a mean of 36.83±16.31 years. Analyze and summary the changes in clinical manifestations, EEG and radiograph of the 20 patients in detail.In the optical microscope and transmission electron microscope observe the pathological changes and ultrastructure of epileptogenic zone. The level of mitochondrial elongation factor (EF-Tumt and EF-Tsmt) in the brain was detected by the methord of immune electron microscopy and immunohistochemistry respectively, the cells and particles of positive expression were observed, compared with the control group in the optical microscope and transmission electron microscope and then analyzed with statistic methods respectively.Results:1. The patients with temporal lobe epilepsy have diverse forms of seizure and their clinical manifestations are complex.12 cases of patients had single attack types and the other 8 cases had different attack types.In detail there were 4 cases of performance for simple partial seizure,14 cases of performance for complex partial seizure and 9 cases of performance for comprehensive attack.20 cases of patients with the preoperative video EEG all had abnormal discharge. The clinical attacks were monitored in 11 cases. The anomalous signals on the head MRI were found in 16 cases of patients in the experiment group, which were corresponding with the abnormal discharge. The anomalous signals mainly included the volume of the seahorses having lessened, the high signals in temporal lobe on the T2 and FLAIR sequence of head MRI, the disorder of seahorse internal structure, lateral ventricle temporal horns having increased, temporal lobe space-occupying changes and so on. In addition, the other 4 cases in the experiment group had no radiological abnormalities.2. There were a good many pathologic and ultrastructural changes in the brain of patients with temporal lobe epilepsy. In the optical microscope the brain cortex was in disorder, the distribution of neurons was uneven and immature neurons were visible. The nuclei were vacuolated and the cytoplasm was less. The neurons became triangular beause of the degeneration. The proliferation and hyperemia appeared in small vascular and glial cells. Lymphocytes and plasma cells infiltrated. In the transmission electron microscope we found the degeneration and necrosis of nerve cells. The nuclear became pyknotic and the nuclear membrane structure wasn't clear. There was much empty bubble in the cytoplasm and mitochondria. The mitochondrial cristae ruptured and the density of cytoplasm also increased. The astrocytes were swelling. In the cytoplasm different sizes of vacuoles appeared. Sometimes the chromatin stayed at the edge of the astrocytes.3. The expression of EF-Tumt and EF-Tsmt positive particles in the 20 patients'brain with refractory temporal lobe epilepsy was higher than that of control group significantly in immune electron microscopy. In the experimental group the number of EF-Tumt positive particles was a mean of 112.76±20.79, compared with that of control group with a mean of 32.67±10.73. We did t-text of two samples and concluded that there was a significant difference(p<0.01) between them. In the experimental group the number of EF-Tsmt positive particles was a mean of 111.48±19.55, compared with that of control group with a mean of 33.5±8.62. The similar conclusion was drawn with the expression of EF-Tumt positive particles.4 In the optical microscope the expression of EF-Tumt and EF-Tsmt proteins was higher in the brain of patients with refractory temporal lobe epilepsy, compared with that of the control group. In the experimental group the number of EF-Tumt positive particles was a mean of 50.99±9.41, compared with that of control group with a mean of 27.87±3.46. In the experimental group the number of EF-Tsmt positive particles was a mean of 53±9.40, compared with the control group with a mean of 27.94±7.05. With the method of t-text we concluded that the difference (p<0.05) between experimental group and control group was statistically significant.Conclusions:1. The patients temporal lobe epilepsy have complex attack forms and clinical manifestations.80% patients in the experimental group had abnormal changes on head MRI. All of them in the experiment were found anomalies in the process of long-term video EEG monitoring.2. There were a good many pathologic and ultrastructural changes in the brain of patients with temporal lobe epilepsy, including the degeneration and necrosis of nerve cells, glial cell hyperplasia, the nucleus with empty bubble, the pyknotic nuclear, cytoplasm vacuoles, mitochondria swelling and so on.3. The expression of EF-Tumt and EF-Tsmt in the 20 patients'brain with refractory temporal lobe epilepsy was higher than that of control group significantly. There were statistical differences between the two groups. The refractory temporal lobe epilepsy was closely correlated with the expression of the mitochondrial elongation factor.4. Innovation points:The animal experiments research has confirmed that the expression of EF-Tumt and EF-Tsmt increased when seizures happened. There has been no research evidence of EF-Tumt and EF-Tsmt in clinical trials until now...